FDA Approval Sought for Prostate Cancer Imaging Product TLX591-CDx

A new drug application (NDA) has been submitted to the FDA for TLX591-CDx (illumet), a radiopharmaceutical product that targets prostate-specific membrane antigen (PSMA), for the imaging of prostate cancer through the use of positron emission tomography, according to an announcement from Telix Pharmaceuticals Limited.¹

The application for the product is comprised of clinical findings collected from over 600 patients who participated in prospective and retrospective clinical trials that were conducted by Telix Pharmaceuticals or in collaboration. The NDA is also based on definitive peer-reviewed clinical research that had been conducted at the University of California, Los Angeles (UCLA), the Peter MacCallum Cancer Centre, and Heidelberg University Hospital.

“We are pleased to have achieved this significant milestone with the submission of the first commercial NDA for PSMA imaging in the United States,” Bernard Lambert, MD, president of Telix Pharmaceuticals USA, stated in a press release. “Telix has engaged with the FDA since July 2019, with valuable guidance resulting in what we believe to be a comprehensive submission. Subject to FDA approval, we look forward to bringing this product to market with our commercial partners to serve the needs of men living with prostate cancer.”

TLX591-CDx is a radiopharmaceutical for the imaging of metastatic prostate cancer. The imaging product comes in a “cold kit” to allow for quick preparation of 68Ga-PSMA-11 injection, rapid radiolabeling at room temperature with high radiochemical purity; it is compatible with the 68Ga generators that are already commercially available.²

The product is being used in research efforts under investigational new drug applications at Emory University Hospital, Memorial Sloan Kettering Cancer Center, and Endocyte.

The pharmaceutical company has also partnered with Cardinal Health, UPPI, and Pharmacologic in the United States for pharmacy preparation purposes, as well as to distribute the kit as an investigational product for use in investigator-sponsored research efforts.

Imaging with 68Ga-PSMA-11 PET has been shown to result in significant changes in the management of biochemically recurrent prostate cancer. In a prospective, single-arm trial, referring physicians applied 68Ga-PSMA-11 PET­–based recommended management changes to 72% (n = 98) of 136 patients.³ 68Ga-PSMA-11 PET resulted in the prevention of unnecessary diagnostic tests and a reduction in the proportion of patients with unknown sites of disease.

The study had included participants with prostate adenocarcinoma and biochemical recurrence. These patients were recruited at UCLA and the University of California, San Francisco. Investigators defined recurrence as a prostate-specific antigen (PSA) level of 0.2 ng/mL or higher at over 6 weeks post prostatectomy or a PSA increase of 2 ng/mL or more above nadir after radiation treatment. The imaging results were interpreted using PROMISE, an image-based TNM staging system.

The study included 3 questionnaires that were completed by the treating physicians. The first was a questionnaire completed upon the patient being scheduled for PSMA PET. The second questionnaire was completed when the PSMA PET report was received. Then, there was a 3- to 6-month follow-up questionnaire that examined whether the intended management was implemented.

Initially, the study recruited a total of 635 participants; however, after excluding those who did not have the pre- and/or post-PET questionnaires, the remaining intended management population was comprised of 382 patients. Approximately half of these patients were then missing the questionnaire from the referring physician, which resulted in an “implemented” management population comprised of 206 patients.

The median age of participants across the cohorts was 70.1 years. In the intended cohort, the median PSA was 1.86. Sixty-two percent of patients had a Gleason score of less than 8, 29% had a score of 8 or more, and 9% were missing data. Initial treatment in this cohort was prostatectomy (44%), radiotherapy (26%), and prostatectomy plus salvage radiotherapy (30%). Other previous treatments included androgen deprivation therapy (ADT; 38%), local salvage therapy (15%), abiraterone acetate (Zytiga) or enzalutamide (Xtandi; 3%), chemotherapy (3%), and bone-targeted therapy (1%).

In the implemented cohort, the median PSA was 1.75 ng mL. Sixty-one percent of patients had a Gleason score of less than 8, 30% had a score 8 or more, and 9% had missing data. Initial treatment in this cohort included prostatectomy (42%), radiotherapy (24%), or prostatectomy plus salvage radiotherapy (34%). Other prior treatments included ADT (39%), local salvage therapy (9%), abiraterone acetate or enzalutamide (2%), and chemotherapy (1%).

In the intended cohort, an intended management change was reported in 68% of participants, with the intended change determined to be “major” in 46% of the patients. In total, 150 diagnostic tests were prevented, comprising mostly CT (n = 43) and bone scans (n =52); however, 68Ga-PSMA-11 PET results did trigger 73 tests per the study protocol. Over half (n = 44) of these tests were biopsies. The imaging outcomes also resulted in a decline from 68% to 29% in the proportion of patients with unknown sites of disease.

For patients with unknown disease site, it was recommended that 47% switch to active surveillance; for those with locoregional disease, it was recommended that 56% switch to local/focal therapy; for those with metastatic disease, it was recommended that 69% of those with M1a and 43% of those with M1bc switch to systemic treatment.

The implementation cohort was comprised of 136 patients for whom changes were intended and 70 patients for whom changes were not. For the former group, the referring physician survey results demonstrated that 72% of the changes were implemented. In the latter group, the referring physician followed the recommendation in 89% of the patients.

“Submitting an NDA to the FDA for our first clinical product is a major commercial inflection point for the Company and follows our European submission earlier this year,” Christian P. Behrenbruch, MBA, chief executive officer of Telix Pharmaceuticals, added in the release. “The Telix team and our advisors have done an outstanding job of preparing this submission, which we believe is founded on compelling clinical evidence that supports broad diagnostic utility in the management of prostate cancer.”

References

1. Telix Pharmaceuticals submits new drug application to US FDA for prostate cancer imaging product. News release. Telix Pharmaceuticals Limited. September 23, 2020. Accessed September 25, 2020. https://bit.ly/3j8bBdC.
2. TLX591 prostate cancer. Telix Pharmaceuticals Limited. Accessed September 25, 2020. https://bit.ly/2S2ANGJ.
3. Ferdinandus J, Fendler WP, Calais J, et al. Impact of 68Ga-PSMA-11 PET on the management of biochemically recurrent prostate cancer in a prospective single-arm clinical trial. 2020 European Association of Urology Virtual Congress. July 17-26, 2020. Abstract 800.